scholarly journals Simian T Lymphotropic Virus 1 Infection of Papio anubis: tax Sequence Heterogeneity and T Cell Recognition

2017 ◽  
Vol 91 (20) ◽  
Author(s):  
James M. Termini ◽  
Diogo M. Magnani ◽  
Helen S. Maxwell ◽  
William Lauer ◽  
Iris Castro ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Lymphotropic Virus ◽  
T Cell Recognition ◽  
Cellular Immune Responses ◽  
Htlv Infection ◽  
Preventive Vaccine ◽  
T Cell Lines ◽  
Cellular Immune ◽  
Major Target

ABSTRACT Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8+ T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. IMPORTANCE It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A preventive vaccine would significantly impact the global burden associated with HTLV infections. Here we provide fundamental information on the simian T lymphotropic virus (STLV) naturally transmitted in a colony of captive baboons. The limited viral sequence heterogeneity in individual baboons, the identity of the viral gene product that is the major target of cellular immune responses, the persistence of viral amino acid sequences that are the major targets of cellular immune responses, and the emergence in vivo of truncated variants in the major target of cellular immune responses all parallel what are seen with HTLV infection of humans. These results justify the use of STLV-infected baboons as a model system for vaccine development efforts.

scholarly journals Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 126
Author(s):  
Lilin Lai ◽  
Nadine Rouphael ◽  
Yongxian Xu ◽  
Amy C. Sherman ◽  
Srilatha Edupuganti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Influenza A ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Post Vaccination ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

Correlates of T-cell–mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4330-4339 ◽  
Author(s):  
Thushan I. de Silva ◽  
Yanchun Peng ◽  
Aleksandra Leligdowicz ◽  
Irfan Zaidi ◽  
Lucy Li ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
T Cell Response ◽  
Viral Control ◽  
Retroviral Infection ◽  
Cellular Immune Responses ◽  
Key Points ◽  
Cellular Immune ◽  
Insight Into

Key PointsHIV-2 viral control is associated with a polyfunctional Gag-specific CD8+ T-cell response but not with perforin upregulation. Our findings provide insight into cellular immune responses associated with a naturally contained human retroviral infection.

scholarly journals Monitoring CD8 T cell responses to NY-ESO-1: Correlation of humoral and cellular immune responses

2000 ◽  
Vol 97 (9) ◽  
pp. 4760-4765 ◽  
Author(s):  
E. Jager ◽  
Y. Nagata ◽  
S. Gnjatic ◽  
H. Wada ◽  
E. Stockert ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Profiling CD8+ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants

Cell Reports ◽  
2021 ◽  
Vol 36 (11) ◽  
pp. 109708
Author(s):  
Hang Zhang ◽  
Shasha Deng ◽  
Liting Ren ◽  
Peiyi Zheng ◽  
Xiaowen Hu ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 26 ◽  
Author(s):  
Georgia Kalodimou ◽  
Svenja Veit ◽  
Sylvia Jany ◽  
Ulrich Kalinke ◽  
Christopher C. Broder ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
G Protein ◽  
Nipah Virus ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune

Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA–NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA–NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA–NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides.

scholarly journals Impaired Cellular Immune Responses During the First Week of Severe Acute Influenza Infection

2020 ◽  
Vol 222 (7) ◽  
pp. 1235-1244 ◽  
Author(s):  
Jackson S Turner ◽  
Tingting Lei ◽  
Aaron J Schmitz ◽  
Aaron Day ◽  
José Alberto Choreño-Parra ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
T Cell ◽  
Immune Responses ◽  
Influenza Infection ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Inflammatory Monocytes ◽  
Cellular Immune

Abstract Background Cellular immune responses are not well characterized during the initial days of acute symptomatic influenza infection. Methods We developed a prospective cohort of human subjects with confirmed influenza illness of varying severity who presented within a week after symptom onset. We characterized lymphocyte and monocyte populations as well as antigen-specific CD8+ T-cell and B-cell responses from peripheral blood mononuclear cells using flow cytometry and enzyme-linked immunospot assays. Results We recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three patients required mechanical ventilation. Influenza-specific CD8+ T-cell responses expanded before the appearance of plasmablast B cells. However, the influenza-specific CD8+ T-cell response was lower in infected subjects than responses seen in uninfected control subjects. Circulating populations of inflammatory monocytes were increased in most subjects compared with healthy controls. Inflammatory monocytes were significantly reduced in the 3 subjects requiring mechanical ventilation. Inflammatory monocytes were also reduced in a separate validation cohort of mechanically ventilated patients. Conclusions Antigen-specific CD8+ T cells respond early during acute influenza infection at magnitudes that are lower than responses seen in uninfected individuals. Circulating inflammatory monocytes increase during acute illness and low absolute numbers are associated with very severe disease.

Characterization of Cellular Immune Responses to a Recombinant Idiotype Vaccine by ELISPOT and Identification of MHC Class I-Restricted T Cell Epitopes by Peptide Mapping.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1409-1409 ◽  
Author(s):  
Cristina M. Bertinetti ◽  
Hendrik Veelken
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Mhc Class I ◽  
B Cell Lymphoma ◽  
Class I ◽  
Fab Fragment ◽  
Cellular Immune Responses ◽  
Idiotype Vaccine ◽  
Cellular Immune

Abstract Induction of tumor-specific immune responses by idiotype vaccination is a promising strategy for biological therapy of indolent B cell lymphomas. In a previous report, we have described immune responses in a subset of patients participating in a phase I clinical trial primarily designed to demonstrate safety and efficacy of a recombinant idiotype vaccine (Veelken et al., ASH abstract #3342, 2003). In this trial, B-NHL patients who had relapsed after standard chemotherapy received repetitive intradermal vaccinations with recombinant idiotype Fab fragment derived from their tumor mixed with lipid-based adjuvant and concurrent subcutaneous GM-CSF at the same site. We now present the final analysis of cellular immune responses in this cohort. Peripheral blood lymphocytes (PBL) were obtained prior to and on various time points during and after vaccinations. Cryopreserved PBL were stimulated twice by autologous dendritic cells (DC) exposed to the autologous Fab protein for cross-presentation as MHC class I-bound peptides. INFγ-secreting cells were subsequently quantified by ELISPOT with Fab-presenting DC. Alternatively, freshly thawed PBL were directly assayed with recombinant Fab by ELISPOT without prestimulation. An increase in the frequency of Fab-responding PBL was detected in 7 of 15 evaluable patients with the prestimulation assay and in 4 of 10 patients by direct quantitation, resulting in a combined cellular response rate of 53% (9 of 17). A cellular immune response showed a trend for correlation with extended progression-free survival (p=0.08). T cell responses were predominantly idiotype-specific since lesser or no increases in IFNγ-secreting cells were detected against light chain- and VH family-matched control Fabs. Interestingly, a much higher base-line reactivity was observed against the control Fabs in comparison to the patient’s lymphoma Fab in four patients, pointing to the possibility of tumor-specific anergy in lymphoma patients that can at least be partially corrected by active immunization. In an effort to identify the MHC class I-presented idiotype-derived peptides, potential binding motifs were defined by reverse immunology with the SYFPEITHI algorithm (www.syfpeithi.de). Ten candidate peptides from the variable and constant region of an immune responder’s idiotype heavy chain were synthesized and evaluated with post-vaccination PBL by ELISPOT without prestimulation. A peptide derived from the CDR2 region showed a significantly higher response compared to an unrelated peptide control (p=0.0013). Additional peptides derived from the FWR1, CDR1, and CDR2 also showed a significant stimulation, but only in comparison to a no peptide control. ELISPOT offers a valuable tool to monitor cellular immune reponses and demonstrates successful induction of tumor immunity in pretreated, tumor bearing and immunosuppressed B cell lymphoma patients. Supported by Deutsche Krebshilfe

Hepatic Tolerance Induction Prevents Inflammatory Responses To Factor IX Expressing Cells at Supplementary Sites of Gene Transfer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3185-3185
Author(s):  
E. Dobrzynski ◽  
F. Mingozzi ◽  
L. Wang ◽  
B. Mingle ◽  
O. Cao ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Gene Transfer ◽  
Immune Responses ◽  
Tolerance Induction ◽  
Cd8 T Cell ◽  
Factor Ix ◽  
Cell Infiltrate ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract The use of gene replacement therapy is an attractive approach for the treatment of the genetic bleeding disorder hemophilia B (caused by mutations in the coagulation factor IX, FIX, gene). A major concern with this type of procedure is the potential for a host immune response to the therapeutic gene product, which would render treatment ineffective. Previously, we observed inflammatory, cytotoxic T lymphocyte, and antibody responses to a human FIX (hFIX) transgene product after intramuscular (IM) delivery via an E1/E3-deleted adenoviral vector (Ad-hFIX) in C57BL/6 mice. Different from this Th1-biased immune response, IM injection of adeno-associated viral (AAV) vector, a Th2-biased, non-inflammatory response led to antibody-mediated neutralization of hFIX expression, without CTL activation. In contrast to these observations on muscle-directed vector administration, hepatic AAV-hFIX gene transfer induced immune tolerance to the transgene product (JCI 111:1347). Lack of anti-hFIX formation was demonstrated even after challenge with hFIX in adjuvant. In order to examine the effect of tolerance induction on CD8+ T cell-mediated cellular immune responses, we performed the following experiments. C57BL/6 mice (n=4 per experimental group) received IM injections of AAV-hFIX vector (serotype 1) in one hind limb and/or Ad-hFIX vector in the contra-lateral leg. In the latter case, inflammation (as determined by H&E histological evaluation), CD8+ T cell infiltrate and destruction of hFIX expressing muscle fibers were obvious in both legs because of the Ad-hFIX mediated activation of CTL to hFIX. CD8+ T cell responses were strongest in Ad-hFIX transduced muscle at day 14 and in the AAV-hFIX leg at day 30. Expression of hFIX as determined by immunohistochemistry became undetectable in Ad-hFIX injected muscle by day 30, but was not completely eliminated in AAV-hFIX transduced muscle. Injection of AAV-hFIX only, did not cause inflammation of muscle tissue or CD8+ cell infiltrate. When the identical experiment was carried out in C57BL/6 mice that were expressing hFIX from hepatic gene transfer via the AAV serotype 2 vector (performed 6 weeks earlier), a substantial increase in systemic hFIX expression was observed after IM administration of the Ad and AAV-1 vectors (again injected into contra-lateral legs). However, a portion of the increased expression was subsequently lost, which correlated with inflammation and CD8+ T cell infiltrate of the Ad-hFIX transduced muscle. Interestingly, no (3/4 mice) or only minor (1/4 mice) infiltrate was observed in AAV-hFIX injected muscles. Consequently, hFIX expression persisted in the AAV, but not the Ad transduced legs. Presumably, CTL responses to adenoviral antigens were sufficient to target Ad-hFIX transduced muscle despite tolerance to the transgene product. In contrast to control mice, hepatic tolerized animals failed to form anti-hFIX after challenge by IM injection of these viral vectors. Moreover, inflammatory and destructive cellular immune responses to the transgene product were successfully prevented by hepatic tolerance induction, indicating that tolerance induced by gene transfer to the liver affects cellular as well as antibody-mediated responses and extents to tissues other than liver.

scholarly journals Magnitude and Quality of Vaccine-Elicited T-Cell Responses in the Control of Immunodeficiency Virus Replication in Rhesus Monkeys

2008 ◽  
Vol 82 (17) ◽  
pp. 8812-8819 ◽  
Author(s):  
Yue Sun ◽  
Sampa Santra ◽  
Jörn E. Schmitz ◽  
Mario Roederer ◽  
Norman L. Letvin
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Rhesus Monkeys ◽  
T Cell Responses ◽  
Viral Control ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Functional Profiles

ABSTRACT While a diversity of immunogens that elicit qualitatively different cellular immune responses are being assessed in clinical human immunodeficiency virus vaccine trials, the consequences of those varied responses for viral control remain poorly understood. In the present study, we evaluated the induction of virus-specific T-cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitude and the functional profile of the virus-specific CD8+ T cells by measuring gamma interferon, interleukin-2, and tumor necrosis factor alpha production. We found that the different vectors generated virus-specific T-cell responses of different magnitudes and with different functional profiles. Heterologous prime-boost vaccine regimens induced particularly high-frequency virus-specific T-cell responses with polyfunctional repertoires. Yet, immediately after a pathogenic simian-human immunodeficiency virus (SHIV) challenge, no significant differences were observed between these cohorts of vaccinated monkeys in the magnitudes or the functional profiles of their virus-specific CD8+ T cells. This finding suggests that the high viral load shapes the functional repertoire of the cellular immune response during primary infection. Nevertheless, in all vaccination regimens, higher frequency and more polyfunctional vaccine-elicited virus-specific CD8+ T-cell responses were associated with better viral control after SHIV challenge. These observations highlight the contributions of both the quality and the magnitude of vaccine-elicited cellular immune responses in the control of immunodeficiency virus replication.

scholarly journals Expression of CCL20 and Granulocyte-Macrophage Colony-Stimulating Factor, but Not Flt3-L, from Modified Vaccinia Virus Ankara Enhances Antiviral Cellular and Humoral Immune Responses

2006 ◽  
Vol 80 (15) ◽  
pp. 7676-7687 ◽  
Author(s):  
R. Chavan ◽  
K. A. Marfatia ◽  
I. C. An ◽  
D. A. Garber ◽  
M. B. Feinberg
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Cellular Immune ◽  
Stimulating Factor

ABSTRACT While modified vaccinia virus Ankara (MVA) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases, its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts. In light of recent data demonstrating that vaccinia viruses, including MVA, preferentially infect antigen-presenting cells (APCs) that play crucial roles in generating antiviral immunity, we hypothesized that expression of specific cytokines and chemokines that mediate APC recruitment and activation from recombinant MVA (rMVA) vectors would enhance the immunogenicity of these vectors. To test this hypothesis, we generated rMVAs that express murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), human CCL20/human macrophage inflammatory protein 3α (hCCL20/hMIP-3α), or human fms-like tyrosine kinase 3 ligand (hFlt3-L), factors predicted to increase levels of dendritic cells (DCs), to recruit DCs to sites of immunization, or to promote maturation of DCs in vivo, respectively. These rMVAs also coexpress the well-characterized, immunodominant lymphocytic choriomeningitis virus nucleoprotein (NP) antigen that enabled sensitive and quantitative assessment of antigen-specific CD8+ T-cell responses following immunization of BALB/c mice. Our results demonstrate that immunization of mice with rMVAs expressing mGM-CSF or hCCL20, but not hFlt3-L, results in two- to fourfold increases of cellular immune responses directed against vector-encoded antigens and 6- to 17-fold enhancements of MVA-specific antibody titers, compared to those responses elicited by nonadjuvanted rMVA. Of note, cytokine augmentation of cellular immune responses occurs when rMVAs are given as primary immunizations but not when they are used as booster immunizations, suggesting that these APC-modulating proteins, when used as poxvirus-encoded adjuvants, are more effective at stimulating naïve T-cell responses than in promoting recall of preexisting memory T-cell responses. Our results demonstrate that a strategy to express specific genetic adjuvants from rMVA vectors can be successfully applied to enhance the immunogenicity of MVA-based vaccines.

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